Antrodia camphorata Wu, Ryvarden & Chang (classified into Polyporaceae, Aphyllophorales) is a parasitic fungus on the endemic species Cinnamomum kanehirai Hay (Lauraceae), which is an endangered species in Taiwan. Because of its endemic unique and rare utility in pharmacology, A. camphorata possesses high values in commercial and research area, and therefore it is the rarest and most expensive wild fungus in Taiwan nowadays.
A. camphorata only grows on the inner heartwood wall of the stem of Cinnamomum kanehirai Hay (Lauraceae) of more than one hundred years old, or on the moist wood surface of dead cowcamphor trees in Taiwan mountain area of 450-2000 m above sea level. A. camphorata grows in a dark, moist and low-temperatured environment with a very slow growth rate. Thus, it takes a quite long time to produce fruiting body in the nature. Wild A. camphorata grows on old cowcamphor trees, producing its fruiting body from the inner wall of the hollow tree stem. The fruiting body of A. camphorata exhibits various morphology, with shapes of sheet, bell, horseshoe, or tower. The color of new-born fruiting body is florid, then turns to white, pale sorrel, hazel, or tan at growing.
Traditionally, this fungus has been used as a Chinese remedy for food and drug intoxication, diarrhea, abdominal pain, hypertension, itching of the skin, and liver cancer (see, for example, Tsai., Z. T.; Liaw, S. L. The Use and the Effect of Ganoderma; Sang-Yun Press: Taichung, Taiwan, 1982; p 116). In current biological studies, the fruiting bodies exhibited immunomodulating, antioxidative, and hepatoprotective effects (Hsiao, G. et al., J. R. J. Agric. Food Chem. 2003, 51, 3302-3308). The cultured mycelia have shown to have anti-inflammatory activity, vasorelaxation, cytotoxic activity against several tumor cell lines, protective activity of oxidative damage in normal human erythrocytes, and anti-hepatitis B virus activity (see, for example, Liu, J. J. et al., Toxicol. Appl. Pharmacol. 2004, 201, 186-193; Hseu, Y. C. et al., Life Sci. 2002, 71, 469-482; and Lee, I. H. et al., FEMS Microbiol Lett. 2002, 209, 63-67).
There are many biologically active materials contained in A. camphorata, such as polysaccharides, triterpenoids, SOD (peroxidase), adenosine, small molecular proteins, vitamins, trace elements, nucleic acids, steroids, pressure stablizing agents and so on. The only chemical study of the cultured mycelia of A. camphorata was conducted by Nakamura et al., found five cytotoxic maleic and succinic acid derivates (Nakamura, N. et al., J. Nat. Prod. 2004, 67, 46-48). Previous chemical studies of the fruiting body of A. camphorata have led to reports of several components including fatty acids, lignans, phenyl derivatives, sesquiterpenes, steroids, and triterpenoids (see, for example, Chen, C. H.; Yang, S. W. J. Nat. Prod. 1995, 58, 1655-1661; Cherng, I. H.; Wu, D. P.; Chiang, H. C. Phytochemistry 1996, 41, 263-267; and Shen, C. C. et al., J. Chin. Med. 2003, 14, 247-258).
In the present invention, we report the isolation and structural elucidation of three new labdane diterpenoids (1-3) from the fruiting body of A. camphorata, that is 19-hydroxylabda-8(17)-en-16,15-olide (1), 3β,19-dihydroxylabda-8(17),11E-dien-16,15-olide (2), and 13-epi-3β,19-dihydroxylabda-8(17),11E-dien-16,15-olide (3), together with four known compounds, 19-hydroxylabda-8(17),13-dien-16,15-olide (4), 14-deoxy-11,12-didehydroandrographolide (5), 14-deoxyandrographolide, and pinusolidic acid. The three novel compounds and four compounds of known structure were evaluated for their neuroprotective effects in an in vitro test system.